Abstract

Objectives：Neuropathic pain (NP) represents a broad scope of various pathological ramifications of the nervous system. Remimazolam is a proved sedative in treating neuropathic pain. Considering the Bradykinin receptor’s vital role and the potentials of Bradykinin receptor B1 (BDKRB1) in the neuropathic pain-signalling pathway, we nominated them as a primary target for remimazolam.

Methods：In this study, rats were injected with complete freund’s adjuvant (CFA) to construct NP models in vivo. BV2 microglia cells were treated with LPS to establish NP model in vitro. qRT-PCR, ELISA, western blot and immunofluorescence were applied to determine gene expression.

Key findings: Our findings revealed that BDKRB1 was overexpressed in NP models in vivo, while R715 (an antagonist of BDKRB1) suppressed the levels of BDKRB1 and inhibited the hyperpathia induced by spinal nerve litigation surgery. Moreover, remimazolam inactivated BDKRB1 signalling via suppressing NF-κB translocation and decreased the release of pro-inflammatory cytokines. Additionally, remimazolam suppressed the translocation of NF-κB, and inhibited autophagic lysosome formation in vivo and in vitro. However, R838 (an agonist of BDKRB1) reversed the effects of remimazolam.

Conclusions: Remimazolam downregulated BDKRB1, inhibited BDKRB1/RAS/ MEK signalling pathway and regulated the autophagic lysosome induction, exhibiting a better outcome in the NP.